eMedicine Specialties > Pediatrics: Genetics and Metabolic Disease > Genetics
Danon Disease: Treatment & Medication
Updated: Jan 6, 2010
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
- Multimedia
Treatment
Medical Care
Patients with Danon disease require frequent follow-up, with particular attention to the potential for atrial or ventricular arrhythmias and congestive heart failure (CHF). As is recommended in patients with hypertrophic cardiomyopathy (HCM), a ventricular septal thickness more than 30 mm is considered a risk factor for a life-threatening event, particularly in this group of patients who often have a poor prognosis for survival beyond their teenage years.24
An implantable cardioverter-defibrillator (ICD) may be indicated. However, in Maron’s study, all 7 patients had ICDs and 5 had lethal arrhythmias that did not convert with ICD therapy.12 However, not all of those patients died from the arrhythmia. In addition, 4 of those 7 actually died of CHF. CHF must be treated according to the hemodynamic cause for the symptoms. For example, patients with HCM have a relatively restrictive physiology with diastolic dysfunction and should be treated accordingly (ie, improving ventricular filling, improved heart rate control, sinus rhythm maintenance, improved diastolic relaxation); whereas, those with a dilated form of cardiomyopathy tend to have a systolic dysfunction problem that may require different treatment (ie, improved afterload reduction and increased contractility).
Surgical Care
Several surgical interventions should be considered in patients with Danon disease. The proper timing of any of these interventions is not known; however, the risk of sudden death in teenage male patients appears to be substantial. This risk may influence decisions about the timing of surgical interventions.
- Implantable loop recorder (ILR)
- This device is implanted under the skin to record any arrhythmias that may happen when cardiovascular symptoms occur.
- The usual indication is an assessment of severe symptoms that occur too infrequently to be recorded by using conventional, external event recorders.
- The battery in one device (Reveal Plus; Medtronic, Minneapolis, MN) lasts for 14 months. It can be automatically activated when the programmed parameters of the device are satisfied. It can also be activated when the patient has symptoms. An activator that the patient carries is placed over the device, and a button is pushed to activate the ILR.
- ICD placement
- After Danon disease and severe hypertrophic changes of the heart are diagnosed, placement of an ICD should be considered. For patients who have the dilated form of cardiomyopathy, ICDs may be indicated because of the degree of their dysfunction and their history of arrhythmias.
- Recommendations from the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT) trial apply to these patients.25
- Furthermore, if the degree of CHF has progressed to New York Heart Association class III or IV with maximal medical therapy (eg, beta-blockers, afterload reduction, spironolactone, diuretics), placement of a biventricular pacing system, usually a biventricular ICD, should be considered.26
- Cardiac transplantation
- Several reports mention patients with Danon disease who underwent cardiac transplantation.17,11,8,19,12
- Cardiac transplant should be considered as long-term treatment because the life expectancy is short.16 Consideration of cardiac transplantation is necessary because of the limited life expectancy of teenaged male patients, who have a high incidence of sudden death. Maron et al even recommend consideration of early transplant.12
- In addition, female patients may need a cardiac transplant because they are not expected to live past their fifth decade.
- Cardiac transplantation is a reasonable treatment for Danon disease despite the presence of muscular problems because the neurologic disability or problems are mild.
Consultations
Because of the severe nature of this disease and the short life expectancy in male patients, extensive counseling and education with the patient and family is important. When an ICD or cardiac transplantation is contemplated, psychiatric counseling may be needed. Dealing with these issues may be particularly challenging if the patient has clinically significant mental retardation.
Consultation with a neurologist is recommended to assess the degree of skeletal myopathy and cognitive deficiencies.
Genetic consultation regarding molecular testing and genetic counseling is important.
Diet
For the most part, no dietary restrictions are necessary for Danon disease. However, when the patient has symptoms of CHF, sodium restriction may be beneficial. Caffeine can potentially aggravate any underlying tachyarrhythmia.
Activity
Competitive athletic activity should be restricted for individuals with Danon disease and cardiomyopathy as recommended in the 36th Bethesda Conference: Eligibility Recommendations for Competitive Athletes With Cardiovascular Abnormalities.27 Exceptions include activities classified as I-A, which include low-intensity sports with low static and low dynamic components, such as billiards, bowling, or golf.
As for noncompetitive activity, leisurely activities (eg, using an exercise bike or treadmill, playing doubles tennis, cycling at low intensity) are permitted in patients with HCM. The premise is that patients engaging in low-intensity activities are more apt than others to respond to the onset of warning symptoms.28
From a neurologic standpoint, male patients with Danon disease may exercise the skeletal muscles. However, they should avoid excessive fatigue, which could cause muscle injury.29
Medication
No cardiac medications resolve the problem of hypertrophic cardiomyopathy (HCM), particularly in Danon disease. However, standard medications for congestive heart failure (CHF) and arrhythmias should be used as they are in other patients with these conditions. For Danon disease with HCM, no medical treatment is indicated unless the patient has symptoms of CHF or angina. On the contrary, patients with dilated cardiomyopathy should be given anti-CHF medications.
No medications are known to resolve or ease the neuromuscular symptoms of Danon disease.
To the authors' knowledge, no reports have demonstrated successful experience with any of the antiarrhythmic agents used in Danon disease. However, treatment of supraventricular tachycardia (SVT) should begin with beta-blockers. Digoxin and verapamil should be avoided when evidence suggests the presence of Wolff-Parkinson-White syndrome. Although ablation may be indicated, other antiarrhythmic medications (eg, propafenone, disopyramide, amiodarone, sotalol) may be helpful to control SVT if ablation is not possible or desired. The beneficial effects or adverse effects of these medications, when used in Danon disease, have not been established.
Diuretic agents
These drugs are indicated for CHF due to systolic or diastolic dysfunction.
Furosemide (Lasix)
Loop diuretic that increases excretion of water by interfering with chloride-binding cotransport system, which, in turn, inhibits sodium and chloride reabsorption in ascending loop of Henle and distal renal tubule. Increases renal blood flow without increasing filtration rate. Onset of action generally within 1-h. Increases potassium, sodium, calcium, and magnesium excretion.
Dose must be individualized to patient. Depending on response, administer at increments of 20-40 mg, no sooner than 6-8 h after previous dose, until desired diuresis occurs. In infants, titrate with 1-mg/kg/dose increments until satisfactory effect achieved.
Diuretics have major clinical uses in managing disorders involving abnormal fluid retention (edema) or in treating hypertension; diuretic action decreases blood volume.
PO administration less potent diuretic effect than IV administration.
Adult
PO: 20-80 mg/dose PO; may uptitrate prn for desired effect; daily dose administered qd or divided in 2-4 doses
IM or IV: 20-40 mg/dose IV/IM; may repeat in 1-2 h; increase 20 mg/dose until desired effect; can be given q6-12h
IV infusion: 0.1 mg/kg IV bolus, followed by 0.1 mg/kg/h continuous IV infusion; not to exceed 0.4 mg/kg/h
Pediatric
Infants and children:
PO: 1-2 mg/kg/d PO divided in 1-4 doses/d; not to exceed 6 mg/kg/dose
IM or IV: 1-2 mg/kg/dose IV/IM q6-12h
IV infusion: 0.1 mg/kg/h continuous IV infusion; may uptitrate to desired effect; generally up to 0.3-0.4 mg/kg/h
Metformin decreases concentrations; interferes with hypoglycemic effect of antidiabetic agents and antagonizes muscle-relaxing effect of tubocurarine; auditory toxicity appears to be increased with coadministration of aminoglycosides; hearing loss of various degrees may occur; may enhance anticoagulant activity of warfarin when taken concurrently; may increase plasma lithium levels and toxicity when taken concurrently
Documented hypersensitivity; hepatic coma, anuria, and state of severe electrolyte depletion
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Frequently monitor serum electrolyte, CO2, glucose, creatinine, uric acid, calcium, and BUN levels during first few months of therapy and periodically thereafter; can cause clinically significant electrolyte loss; may cause ototoxicity
Spironolactone (Aldactone)
Potassium-sparing diuretic. Indicated for management of edema resulting from excessive aldosterone excretion. Competes with aldosterone for receptor sites in distal renal tubules, increasing water excretion while retaining potassium and hydrogen ions.
Adult
25-200 mg/d PO qd or divided bid
Pediatric
1.5-3.5 mg/kg/d PO qd or divided qid
May decrease effect of anticoagulants; potassium and potassium sparing diuretics may increase toxicity of spironolactone
Documented hypersensitivity; anuria, renal failure or hyperkalemia
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in renal and hepatic impairment; monitor potassium levels
Beta blockers
These agents are indicated for the management of dilated cardiomyopathy.
Carvedilol (Coreg)
Used only for patients with dilated cardiomyopathy and CHF. Nonselective beta- and alpha-adrenergic blocker. Also has antioxidant properties. Does not appear to have intrinsic sympathomimetic activity. May reduce cardiac output and decrease peripheral vascular resistance.
Adult
Individualize dose for each patient
3.125 mg PO bid for 2 wk initially; if tolerated, can be doubled to 6.25 mg bid; to increase q2wk to 25 mg PO bid; not to exceed 50 mg bid
Pediatric
0.08 mg/kg/dose PO bid initially; increase as tolerated q2wk over next 12 wk; not to exceed 0.5 mg/kg/d divided bid
Some children <3.5 y may need tid dosing because of rapid elimination
Rifampin, barbiturates, cholestyramine, colestipol, NSAIDs, salicylates, and penicillins may decrease effects; may increase effects of antidiabetic agents, digoxin, and calcium channel blockers; concurrent administration with clonidine may increase blood pressure and decrease heart rate; may decrease effect of sulfonylureas; cimetidine, fluoxetine, paroxetine, and propafenone may increase levels
Documented hypersensitivity; hypotension; bradycardia; disease of the atrioventricular and/or sinoatrial nodes; cardiogenic shock; overt cardiac failure
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Pregnancy category C in first trimester and category D during second and third trimesters; caution in CHF treated with digitalis, diuretics, or ACE inhibitors (atrioventricular conduction may be slowed); discontinue if liver impairment occurs; caution in peripheral vascular disease, hyperthyroidism, and diabetes mellitus
Metoprolol (Lopressor)
Indicated for dilated cardiomyopathy. Selective beta1-adrenergic receptor blocker that decreases automaticity of contractions.
Adult
PO: 50-100 mg/d PO qd or divided bid
IV: 5 mg IV q5min for 3 doses; if tolerated, may give 100 mg PO qd; carefully monitor blood pressure, heart rate, and ECG during IV administration
Pediatric
Children: 0.1-0.2 mg/kg/dose PO qd/bid
Adolescents: 25 mg/d PO initially; may uptitrate prn and as tolerated to 25-50 mg PO qd/bid
Aluminum salts, barbiturates, NSAIDs, penicillins, calcium salts, cholestyramine, and rifampin may decrease bioavailability and plasma levels, possibly decreasing pharmacologic effects; toxicity may increase with coadministration of sparfloxacin, phenothiazines, astemizole, calcium channel blockers, quinidine, flecainide, and contraceptives; may increase toxicity of digoxin, flecainide, clonidine, epinephrine, nifedipine, prazosin, verapamil, and lidocaine
Documented hypersensitivity; uncompensated CHF, bradycardia, asthma, cardiogenic shock, and atrioventricular conduction abnormalities
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Pregnancy category C in first trimester and category D during second and third trimesters; beta-adrenergic blockade may reduce signs and symptoms of acute hypoglycemia and clinical signs of hyperthyroidism; abrupt withdrawal may exacerbate symptoms of hyperthyroidism, including thyroid storm; closely monitor patient and withdraw drug slowly; during IV administration, carefully monitor blood pressure, heart rate, and ECG
ACE inhibitors
These agents reduce afterload in dilated cardiomyopathy and/or CHF.
Enalapril (Vasotec)
Prevents conversion of angiotensin I to angiotensin II (potent vasoconstrictor), increasing levels of plasma renin and reducing aldosterone secretion. Helps control blood pressure and proteinuria. Decreases pulmonary-to-systemic flow ratio in catheterization laboratory and increases systemic blood flow in patients with relatively low pulmonary vascular resistance. Favorable clinical effect when administered over a long period. Helps prevent potassium loss in distal tubules. Body conserves potassium; therefore, less PO potassium supplementation needed.
Patients who develop a cough, angioedema, bronchospasm, or other hypersensitivity reactions after starting ACE inhibitors should receive an angiotensin-receptor blocker.
Adult
2.5-5 mg/d PO initially; may increase as tolerated; typical dosage 10-40 mg/d PO divided in 1-2 doses
Pediatric
Infants and children: 0.1 mg/kg/d PO qd or divided bid; not to exceed 0.5 mg/kg/d
Older children and adolescents: Administer as in adults
NSAIDs may reduce hypotensive effects; ACE inhibitors may increase digoxin, lithium, and allopurinol levels; rifampin decreases levels; probenecid may increase levels; diuretics may enhance hypotensive effects of ACE inhibitors when given concurrently
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Pregnancy category C in the first trimester and category D during second and third trimesters; caution in renal impairment, valvular stenosis, or severe CHF
Captopril (Capoten)
Prevents conversion of angiotensin I to angiotensin II (potent vasoconstrictor), lowering aldosterone secretion. Rapidly absorbed, but bioavailability significantly reduced with food intake. Peak concentration in 1 h; has short half-life. Cleared by kidney. Can be started at low dose and uptitrated prn and as patient tolerates.
Impaired renal function requires reduced dosage. Absorbed well PO. Give at least 1 h before meals. If added to water, use within 15 min.
Accepted as essential part of any antifailure therapy; provides symptomatic improvement and prolongs survival.
Adult
6.25-25 mg PO bid/tid; increase by 25 mg prn q1-2wk; not to exceed 450 mg/d divided tid
CrCl 10-50 mL/min: Decrease to 75% of starting dosage
CrCl <10 mL/min: Decrease to 50% of starting dosage
Pediatric
Infants: 0.15-0.3 mg/kg/dose PO q6-24h; may uptitrate dose; not to exceed 6 mg/kg/d in 2-4 divided doses prn
Children: 0.3-0.5 mg/kg/dose PO q6-24h; may uptitrate dose; not to exceed of 6 mg/kg/d in 2-4 divided doses prn
Older children and adolescents: Administer as in adults
Decrease dose in renal impairment
NSAIDs may reduce hypotensive effects; ACE inhibitors may increase digoxin, lithium, and allopurinol levels; rifampin decreases levels; probenecid may increase levels; diuretics may enhance hypotensive effects of ACE inhibitors when given concurrently
Documented hypersensitivity; renal impairment
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Pregnancy category C in the first trimester and category D during second and third trimesters; may cause hypotension and reflex tachycardia;
may develop dry cough; caution in renal impairment (decrease dose), valvular stenosis, or severe CHF
More on Danon Disease |
| Overview: Danon Disease |
| Differential Diagnoses & Workup: Danon Disease |
 Treatment & Medication: Danon Disease |
| Follow-up: Danon Disease |
| Multimedia: Danon Disease |
| References |
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References
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Further Reading
Keywords
Danon disease, Danon syndrome, Danon's disease, Danon's syndrome, glycogen storage disease, hypertrophic cardiomyopathy, muscular dystrophy, Wolff-Parkinson-White syndrome, mental retardation, congestive heart failure, sudden death, symptoms
